PUBLICATION
Zebrafish spinal cord oligodendrocyte formation requires boc function
- Authors
- Kearns, C.A., Walker, M., Ravanelli, A.M., Scott, K., Arzbecker, M.R., Appel, B.
- ID
- ZDB-PUB-210601-15
- Date
- 2021
- Source
- Genetics 218(4): (Journal)
- Registered Authors
- Appel, Bruce, Kearns, Christina, Ravanelli, Andrew M.
- Keywords
- Sonic hedgehog, glia, myelin, neural progenitors, oligodendrocyte precursor cells
- MeSH Terms
-
- Animals
- Neural Cell Adhesion Molecules/genetics
- Neural Cell Adhesion Molecules/metabolism*
- Neural Stem Cells/cytology
- Neural Stem Cells/metabolism
- Neurogenesis*
- Oligodendroglia/cytology
- Oligodendroglia/metabolism*
- Spinal Cord/cytology
- Spinal Cord/embryology
- Spinal Cord/metabolism*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 34057474 Full text @ Genetics
Citation
Kearns, C.A., Walker, M., Ravanelli, A.M., Scott, K., Arzbecker, M.R., Appel, B. (2021) Zebrafish spinal cord oligodendrocyte formation requires boc function. Genetics. 218(4):.
Abstract
The axis of the vertebrate neural tube is patterned, in part, by a ventral to dorsal gradient of Shh signaling. In the ventral spinal cord, Shh induces concentration-dependent expression of transcription factors, subdividing neural progenitors into distinct domains that subsequently produce distinct neuronal and glial subtypes. In particular, progenitors of the pMN domain express the bHLH transcription factor Olig2 and produce motor neurons followed by oligodendrocytes, the myelinating glial cell type of the central nervous system. In addition to its role in patterning ventral progenitors, Shh signaling must be maintained through development to specify pMN progenitors for oligodendrocyte fate. Using a forward genetic screen in zebrafish for mutations that disrupt development of oligodendrocytes, we identified a new mutant allele of boc, which encodes a type I transmembrane protein that functions as a coreceptor for Shh. Embryos homozygous for the bocco25 allele, which creates a missense mutation in a Fibronectin type III domain that binds Shh, have normally patterned spinal cords but fail to maintain pMN progenitors, resulting in a deficit of oligodendrocytes. Using a sensitive fluorescent detection method for in situ RNA hybridization, we found that spinal cord cells express boc in a graded fashion that is inverse to the gradient of Shh signaling activity and that boc function is necessary to maintain pMN progenitors by shaping the Shh signaling gradient.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping